Disposition kinetics of dibekacin in patients with renal failure and in patients undergoing hemodialysis

Abstract

Dibekacin pharmacokinetics was studied in 3 healthy volunteers, 5 patients with renal failure presenting Cl(cr), between 4.0 and 67 ml min-1 per 1.73 m2 of body surface and 5 anephric patients given as a 30 minute intravenous infusion. The antibiotic was assayed in plasma and urine by means of a high performance liquid chromatography (HPLC) method. A two compartment kinetic model was used to describe the bi-phasic decline of plasma concentration and to calculate the different pharmacokinetic parameters. Slow disposition and elimination rate constants β and k10 respectively, and total body clearance were markedly diminished in anephric patients (p << 0.001): t1/2β = 2.12 h, k10 = 0.642 h-1 and Cl = 0.882 ml/min per kg, in normal subjects and t1/2β = 4.73 h, k10 = 0.278 h-1 and Cl = 0.693 ml/min per kg in anephric patients. The apparent volumes of distribution increased while the creatinine clearance of the patients decreased. Thus Vd((area)) of volunteers with normal renal function was